Long non‑coding RNA NEAT1 promotes migration and invasion of oral squamous cell carcinoma cells by sponging microRNA‑365

Abstract

Long non-coding RNA nuclear enriched abundant transcript 1 (NEAT1) has been demonstrated to serve key roles in numerous human cancer types, but its function in oral squamous cell carcinoma (OSCC) and underlying regulatory mechanism have not been evaluated. The present study demonstrated that expression of NEAT1 was significantly higher in OSCC tissue and cell lines compared with adjacent non-tumour tissue and normal oral keratinocytes, respectively. Additionally, upregulation of NEAT1 was significantly associated with advanced clinical stage and shorter survival time in patients with OSCC. Bioinformatics analysis and luciferase reporter gene assay data confirmed the interaction between NEAT1 and miR-365, and it was revealed that NEAT1 may downregulate microRNA (miR)-365 expression in OSCC cells. Furthermore, inhibition of NEAT1 expression led to a significant reduction in OSCC cell migration and invasion, which was accompanied by reduced matrix metalloproteinase (MMP)-2 and MMP9 protein expression. By contrast, inhibition of miR-365 eliminated suppressive effects of NEAT1 knockdown on OSCC cell migration and invasion. miR-365 was significantly downregulated in OSCC tissue and cell lines and an inverse correlation between miR-365 and NEAT1 expression in OSCC tissue was observed. To conclude, the present study demonstrated that NEAT1 promoted migration and invasiveness of OSCC cells by sponging miR-365. The current study suggests that NEAT1 may serve as a novel therapeutic target for the treatment of OSCC.

World Workshop on Oral Medicine VII: Clinical evidence of differential expression of lncRNAs in oral squamous cell carcinoma: A scoping review

“…Univariate Kaplan–Meier analyses also found the expression of several other lncRNAs to be positively correlated with poorer survival in OSCC including MALAT1 ( p < 0.05, 54 patients) (Zhou et al., ), NEAT1 ( p = 0.042, 58 patients and p = 0.01, 30 patients) (Huang, He, et al., ; Liu, Shang et al., ), LINC00668 ( p < 0.05, 50 patients) (Zhang, ), FTH1P3 ( p = 0.0032, 70 patients) (Zhang, ), CCAT2 ( p = 0.028, 62 patients) (Ma et al., ), PDIA3P ( p = 0.0211, 58 patients) (Sun et al., ) and ANRIL ( p = 0.013, 130 patients) (Chai, Yuan, Chen, Zhou, & Wu, ). When analysing only TSCC patients, higher expression associated with poor OS was found for GIHCG ( p < 0.05 from a 20 patients cohort) (Ma, Wang, Gong, Xue, & Zuo, ).…”

“…In 2013, Tang et al (2013) reported that in the presence of nodal involvement the expression of HOTAIR, NEAT1 and UCA1 was significantly upregulated, while MEG3 was downregulated. Two subsequent studies investigating 58 and 30 OSCC patients respectively confirmed that NEAT1 overexpression is significantly correlated with nodal metastasis (p = 0.009) (Huang, He, et al, 2018;Liu, Shang et al, 2018) and two studies addressing TSCC confirmed UCA1 overexpression (p = 0.0379 and p = 0.011 when addressing 94 and 124 patients, respectively) (Fang et al, 2014;Yang et al, 2016). One author hypothesized that UCA1 overexpression promoted the metastatic but not the proliferative ability of TSCC cells (Fang et al, 2014).…”

“…() in OSCC, one on a TSCC cohort of 94 patients (Fang et al., ) and another on a report addressing TCGA data (Zou et al., ), failed to establish NEAT1 and HULC as DE. Two studies, investigating 58 and 30 OSCC patients respectively, found a significant overexpression of NEAT1 (Huang, He, & Wei, ; Liu, Shang, & Zheng, ). Interestingly, these results demonstrated a downregulation of NEAT1 in the presence of dysplasia, thus suggesting a potential shift in its expression during tumorigenesis (Gibb et al., ; Jia, Wang, & Sun, ).…”

MicroRNA-592 suppresses the malignant phenotypes of thyroid cancer by regulating lncRNA NEAT1 and downregulating NOVA1

“…NOVA1, a member of the NOVA family of neuron-specific RNA-binding proteins, is aberrantly downregulated in multiple human cancers and affects a variety of pathophysiological processes associated with carcinogenesis and cancer progression (50)(51)(52). The expression and roles of NEAT1 and roles have been studied in other human cancers (43)(44)(45)(46)(47)(48)(49). Herein, we identified a novel NEAT1-miR-592-NOVA1 pathway, and this pathway could serve crucial roles in the aggressiveness of thyroid cancer.…”

“…In the present study, NOVA1 was validated as a direct target of miR-592 in thyroid cancer cells, and NEAT1 was proposed to function as a ceRNA to modulate NOVA1 expression by sponging miR-592. Multiple studies reported that NEAT1 is expressed at high levels and exerts oncogenic roles in a variety of human cancers, including cervical cancer (43), nasopharyngeal carcinoma (44), breast cancer (45), non-small cell lung cancer (46), colorectal cancer (47,48), and oral squamous cell carcinoma (49). NEAT1 is also upregulated in thyroid cancer (35)(36)(37), and upregulation of NEAT1 is positively correlated with TNM stage and tumor size (35).…”